IL37476A - 6-(1,2,5-thiadiazolyloxyacetyl)-aminopenicillanic acids and their preparation - Google Patents

Description

acids and their preparation GYAfiA 2 The object of the invention is a process for the preparation of new It is known in the art that the derivatives of acid have an effect similar to of natural penicilline Erhart an effect can be considerably influenced by varying the acyl It has been f ound that ne penicillines of the general formula X or a are highly effective i inhibiting the growth of they very which is of great advantage i oral She term is employed here to indicate straight or branched alkyl groups containing from 1 to 4 carbon for example ethyl or propyl The invention relates to novel penioillinee of the general formula I whioh are prepared by reacting nioillanio s o anhydrous m II or a reaotive derivative thereof in the S and X have the same meaning as above and the penioillinee ΘΟ are if in the form of their In a preferable mode of realization of the prooess aooording to the inventio one oan employ the des aoid acid the preferably mixed anhydrides of the acids of the general mula The mixed anhydrides be prepared from arbox acids and aoid As aoid ester one oan emplo J the of aoid as in which case the decomposition of the aoylated duct is carried out in a known manner with water or Acylatiort may be performed in the presence absenoe of bbdiimide euoh as for example or the The acids the substituted in 4 used for the preparation penicillines according to the are new They may be obtained for exnmnle from the known einstook 2823 British Patent Specification 1 154 It has been found that acids of the general formula II may be readily prepared from with carboxylic In the course of these reactions one The novel oompounds according to the invention ve a highly active effect on Their range of antibacterial effect compares with that More all of these compounds have a Iced bacteriostatic effect on gram positive cocci Streptococcus Streptococcus Diplococcus and on gram negative cocci also on gram positive spore bacteria strains Titration of the substances was performed with the as well as with the diffusion The following table indicates the results thus arrived Strains Sensitivity to Penicillines oxacilline 2 3 4 lowest inhibiting conce Streptococcus pyogenes 80 077 S OKI 80 078 S OKI 30 079 S OKI 80 080 S pyog 1 pyog 2 pyog 3 pyog 4 s pyog 5 s Strains Sensitivity to Penicillines 1 2 3 4 lowest inhibiting concent Streptococcus viridans R S 1 s 2 s 3 s 4 s 5 s 31 6 50 7 R Strains Sensitivity to Penicillines 2 3 lowest iniiibiting concentr Streptococcus faecalis Strains Sensitivit to 2 3 lowest conce Diplococc s pneumoniae Strains Sensiti ity to Penicillines 1 3 4 lowest inhibiting concentr Neisseria S S s s s 1 Pharyngo 2 Pharyngo 3 Strains Sensitivity to Penicillines oxacilline 1 2 3 4 lowest inhibiting concentr Cereus bacillus OKI 100 Subtilis R 5 OKI 100 008 Subtilis S OKI 101 020 Subtilis s 6 OKI 101 021 Subtilis s Subtilis S 196S Subtilis S 5 6 25 1969 R Cereus 1 S 12 5 5 Cereus 2 S Subtilis R iations S sensitive fairly sensitive resistent 3 4 o 5 The method according to the invention is described below more particularly the following illustrative 1 EXAMPLE g of tic acid dissolved in dry acetone were treated at with moles of At the same temperature a solution of g of ter in 20 ml of acetone were added dropwise in 5 the reaction mixture was stirred for 20 wherafter the temperature was raised to g of were ded in 15 ml of at and the mixture was dissolved by adding moles of The on so obtained was added the reaction then red for 1 hour in the temperature range of diluted with 120 ml of water and acidified pH 2 by adding 10 ml of n hydrochloric The fiction mixture was ted a mixture 50 ml of ethylacetate and 50 ml of isopropylethe then with ml of The nic phase was washed with 3 x 50 ml of and dried over iodine solution for 10 mg of the Example 2 To a mixture of 50 ml of dry benzene and 5 g of with an of and L in and 1 drop of pyridine a solution of ml of thionylohloride in 10 ml of benzene were added in the course of 30 with After boiling the mixture for 30 the benzene was distilled off at atmospheric and the residual acidic chloride was freed from solvent i g of a yellow oil were g of acid were suspended in 60 mi of water at then dissolved by adding of sodium hydrocarbonate and diluted with 40 ml of The cetone solution of the acide chloride was added to the sodium salt solution dropwise 5 minutes at The the solution was in the range of to 8 by ding some of sodium The solution was then diluted with 50 ml of extracted with 2 x 50 ml of and acidified with 10 ml of 5 phosphoric The racemic acid mixture was extracted with re of 50 of ether and 50 ml of ethyl the organic lodometric analysis showed a consumption of ml of iodine solution for 10 mg of the Example 4 repare of ml 16 insufficientOCRQuality

Claims (1)

A process for the preparatio of new penlclllines and salts thereof of the general I wherein A stands for phenyl or B stands for hydrogen or a and stands for hydrogen or a alkyl which comprises reacting acid or a salt or an an aqueous or anhydrous with a carboxylic acid of the general formula II or a reactive derivative thereof in t he and X have the same meaning as above and the penlclllines so obtained are if in the form of their Compounds of the general formula I Claim 1 and their 17 aoid salts acid and salts acid and salts acid and salts A process the preparation of human or veterinary comprising the step of mixing a compound of the I in

1. Claim 1 or a salt as active with organic or solid or liquid Carrie dilutin Human and veterinary pharmaceutical compositions as active agent compounds of the general formula I in Claim insufficientOCRQuality